Synthesis and Characterization of a Positron Emission Tomography Imaging Probe Selectively Targeting the Second Bromodomain of Bromodomain Protein BRD4.
Bioconjug Chem
; 32(8): 1711-1718, 2021 08 18.
Article
in En
| MEDLINE
| ID: mdl-34139120
ABSTRACT
Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target. Positron emission tomography (PET) imaging could allow us to achieve in-depth knowledge of the BD2 bromodomain. Herein we describe the radiosynthesis and evaluation of [11C]1 as a BRD4 BD2 bromodomain PET imaging radioligand. Our preliminary PET imaging results in rodents demonstrated that [11C]1 had suitable biodistribution in peripheral organs and tissues. Further blocking studies indicated that [11C]1 had good binding specificity toward the BD2 bromodomain. This study may pave the way for the development of a PET radioligand specifically targeting BD1/2 bromodomains as well as for the biological mechanism investigation of BD1/2 bromodomains.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Nuclear Proteins
/
Drug Delivery Systems
/
Positron-Emission Tomography
/
Isotope Labeling
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Bioconjug Chem
Journal subject:
BIOQUIMICA
Year:
2021
Type:
Article